The Moos Room™

4-5-24 - Dr. Joe walks through a brief history of Influenza A in cattle courtesy of an excellent review paper.

Influenza A in Bovine Species: A Narrative Literature Review

USDA APHIS - Website with access to FAQ, Recommendations, and Testing Guide

CDC Announcement - 4-1-24

MN Board of Animal Health - Website

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Hosted by members of the University of Minnesota Extension Beef and Dairy Teams, The Moos Room discusses relevant topics to help beef and dairy producers be more successful. The information is evidence-based and presented as an informal conversation between the hosts and guests.

Dr. Joe Armstrong:

What is up, everybody? This is doctor Joe Armstrong. It is 9 AM on April 5th. Before we get going on today's topic, we're going to update briefly on what states we have affected by the current situation. The updated list as of 9 AM on April 5th 2024 is Texas, New Mexico, Kansas, Idaho, Michigan, and Ohio.

Dr. Joe Armstrong:

Those are the states that are currently being reported by USDA. Are other states impacted? Most likely. But we do not have official, confirmed test results to tell us that yet. So one other thing that we need to mention before we move on.

Dr. Joe Armstrong:

There's been a lot of coverage of states requiring new things for cattle to enter the state, whether that's a permit or I've seen in popular press a passport. Nebraska is one of those states. They are requiring a permit number for breeding female dairy cattle entering the state. That is not a big deal, and it is not certainly worthy of news attention in my opinion. It is purely a heightened state of being able to track things in real time.

Dr. Joe Armstrong:

If you have to call to get a permit number, they know exactly when cattle are moving. As opposed to if you write a CVI, which stands for a certificate of veterinary inspection or commonly known as a health paper, that can sit and not have to be turned in for a couple weeks in a veterinary clinic's outgoing mailbox. So all it is is just trying to be on top of the game where we're saying, right, we want to know what's moving in real time or at more in real time than if we're waiting a week or two to get papers mailed to us. That's it. So why aren't you hearing about Minnesota doing this?

Dr. Joe Armstrong:

It's because they already require it. If you're going to use a paper CVI, you need to have a permit number. If you're gonna use an electronic CVI, because we can have that happen very quickly and we don't have to wait on mail, you don't need a permit. So we're already taking care of that in Minnesota. That's why we're not hearing a bunch about it in Minnesota because we already require that.

Dr. Joe Armstrong:

Just wanted to get that cleared up because I did get a couple questions about that. Alright. Let's dive into the real topic today. We are going to take a tour on the history of influenza a in cattle. So as some basic background, when we talk about influenza viruses, we talk about them in 4 types, a, b, c, and d.

Dr. Joe Armstrong:

After type, they're broken into subtype, and then after subtype, they're broken into clade, and then there are subclades. So in our current situation, the HPAI like virus that has been in cattle and in the news is a Type A, Subtype H5N1, and the clade is 2.3.4 .4 b. So in the interest of time, today we're going to talk about 2 of the types, type a and type d. I don't think in the purpose of talking about cattle, we're missing a whole lot if we skip types b and c. There is some data showing type c in cattle connected with a feedlot study.

Dr. Joe Armstrong:

But for our current situation, I don't think it adds a ton to the conversation right now. So in general, until the discovery of type d influenza, we thought cattle were largely unaffected by influenza viruses. So in 2011, they isolated a influenza virus from a sick piglet in Oklahoma. But after looking into further study to look at seroprevalence and, and where this virus truly lives, it was determined that cattle are indeed the primary reservoir. Now that was a quite surprising discovery because, like I said, we were under the impression that cattle were largely unaffected by influenza viruses.

Dr. Joe Armstrong:

And now we're finding that they're actually a primary reservoir, and we had to make a new type just for their influenza virus. So that was back in 2011. We find a new type of influenza virus, and we find that it primarily lives in cattle. Now finding an influenza virus where the primary reservoir and host is cattle opens the door. It says, well, if they're the primary reservoir for an influenza virus, and we didn't even think they were impacted before, it certainly suggests that they could be susceptible to the other types of influenza.

Dr. Joe Armstrong:

Initially, when all of this started, I was a little surprised. And the more I read about influenza A, I'm realizing that I should not have been as surprised as I was. Now let's throw out some fun facts because I I think it's nice to throw some of those in into a serious conversation every once in a while. And for this, there is some context that matters. When we look at 2 species or look at swine and bovine, cattle have been domesticated by humans for about 10,500 years, and pigs have been domesticated by humans for about 9000 years.

Dr. Joe Armstrong:

Now why do I bring that up? Well, both species have been integral to our cultures and communities for a long time, and there are plenty of interactions between humans and pigs and humans and cattle. Influenza A has really carved out a niche at that human animal interface. That's where it likes to live. Pigs have long been mixing vessels for both avian and human influenza a viruses, and that transmission is bidirectional.

Dr. Joe Armstrong:

So why is that the case for pigs, which have been domesticated for 9000 years, but not the case for cattle that have been domesticated even longer? Why have cattle largely been spared from influenza A when it has pretty much infected every species you can think of. So there's a long list of research looking at specific things about bovines that could contribute to this. On the list is bovine colostrum, bovine lactoferrin, serum inhibitors, certain bovine lung factors. There's also proteins that bovines have that have antiviral properties.

Dr. Joe Armstrong:

We don't have time to get into it, and, honestly, the research isn't super definitive. There's just something special about cows, which we already knew. And if you're listening to this podcast, you likely agree. What we need to look at next is, have we seen influenza a viruses in cattle before? In the US, the answer is no, but we're not the only country in the world.

Dr. Joe Armstrong:

There's plenty of research that happens other places, and it's valuable to look outside of our little bubble. So if I walk through the list, looking at this review paper that I will post in the show notes for everyone to read if they would like, I'm looking at specifically identified influenza a virus in cattle, evidence of the virus itself, or serology. So serology is looking for antibodies against something. So we're looking for antibodies that tell us about the presence of that virus at some point. So in the early 19 seventies, we have isolation and identification of an influenza a virus from cattle in Russia.

Dr. Joe Armstrong:

Shortly after that, 1 year later, that was in 1973. In 1974, we have isolation of influenza a virus strains from nasal swabs and lung samples from acutely ill cattle in Hungary. Those cattle in Hungary had coughs, nasal discharge, watery eyes, anorexia and lethargy, and many of them died. Most of that impacted population was calves that were 4 to 6 months old. After that, we take a big jump all the way to the late nineties before we see it pop up again.

Dr. Joe Armstrong:

So in 1997, in Southwest England, cows were experiencing a sporadic drop in milk production, and a researcher reported seroconversion, so they had antibodies against influenza a virus in cattle from Great Britain, and that was also associated with reduced milk and respiratory disease. They were unable to isolate the virus at that time. What is most interesting about that particular research is that they had the forethought to say, okay, we are getting antibodies against influenza a, but is it what is actually causing the disease? So they checked for antibodies against the other major pathogens, BVD, IBR, PI3, and BRSV. And they found no titers, or no high levels of antibodies against those viruses, and that suggests that influenza a was the sole cause.

Dr. Joe Armstrong:

So in 1999, also in England, they had reported natural cases of influenza in milking cows with an annual incidence of 10 to 20% in some herds. And the list of symptoms that they are reporting from that situation are a sudden drop in milk, mild fever, anorexia or not eating, occasional respiratory signs, nasal discharge, and some increased respiratory rates. That sounds eerily familiar to what we're dealing with now. When they looked further and they looked at serologic screening, they paired sera from 5 herds, and they showed that there were antibodies against BRSV and PI3 in all the herds, there was BVD and IBR antibodies in only some of the herds, but also, only 5% of the cattle were seronegative for both strains they were looking at of influenza a. So in that situation, only 5% of the cattle were negative for antibodies against influenza a.

Dr. Joe Armstrong:

Another study from the same area of the world, 1998 and 1999, Northern Ireland, 84 paired acute and convalescent sera collected from 17 outbreaks, characterized by respiratory disease, diarrhea, and milk drop. In that study, they were looking at 2 different strains of influenza A virus. 57% of the cows were positive for antibodies against the one strain, and 59% were positive against the other strain they were looking at, both influenza a viruses. Then we jump to 2,008. We have a researcher that showed that they had rising antibody titers against an influenza a virus in a Holstein Friesian herd in southwest England.

Dr. Joe Armstrong:

That researcher also looked at antibody titers against BRSV, BVD, IBR, and PI 3 and found that they were seronegative, so they did not have antibodies against those viruses, suggesting that influenza a was the sole cause. So looking at this evidence of influenza A in cattle, it's different than what we're dealing with now in the current time because there have been different subtypes that they've been looking for. Primarily, they've been looking at h1n1 and h3n2, And right now, what we're detecting in cattle is h5n1. So what's the point of talking through this and explaining the history of influenza A in cattle? Like I said before, cattle have something different about them that so far has kept them from being involved in the influenza a conversation.

Dr. Joe Armstrong:

For 10,500 years, they've avoided primarily becoming part of that interaction. So the purpose of going through this is to make sure that we understand that potentially, this situation has occurred before in some form, and to my knowledge, did not result in a catastrophe. Alright. Let's move on to some studies that look at influenza a and specifically trying to infect or inoculate calves. So one of the studies that they mention in this review article is actually taking a high path avian influenza virus and purposely inoculating a group of calves in an experimental setting.

Dr. Joe Armstrong:

So this was done in a high containment animal facility where they took 6 3 month old calves and purposely inoculated them in the nose with high path avian influenza. What they were looking for was will they develop an immune response, will they develop antibodies and seroconvert after seeing this virus? In addition to that, they also placed 2 calves in with them as contact animals to see if it could then move from those calves to the contact animals. Here's where it gets a little tricky. All 6 calves that were inoculated did seroconvert, they developed antibodies.

Dr. Joe Armstrong:

But based on the testing, it was a little dicey on whether or not it did move to a contact animal. The statement specifically from the paper is that the possibility that the infectivity detected in the contact calf at one day post inoculation was a result of residual inoculum cannot be ruled out. So there was 2 contact calves in this study, and what they're saying is that they detected some infectivity in one of the contact calves one day after they inoculated the original 6. And what they're saying is that it's possible that that calf was actually just infected by the actual inoculum that was still present in those calves, and that the contact calf did not acquire the virus after it had circulated in the inoculated calves, they just also became an inoculated calf because they got some of the inoculum from the nasal passage of the inoculated calves. Important to note in this study, all of the calves in the study never displayed any clinical signs of disease.

Dr. Joe Armstrong:

If we fast forward just a tiny bit to 2010, we have a paper that takes a type a influenza strain that is h three n eight and infects 6 beef calves and 2 ponies with that. In that study, the calves did not have any viral shedding, did not display any clinical symptoms or disease compared to the ponies. Last thing I wanna talk about before we get to my final thoughts. When we look at other countries and specifically relationships between birds and cattle, we find some pretty cool relationships in nature. One of them is the cattle egret.

Dr. Joe Armstrong:

We're gonna talk about cattle egrets in Egypt. So cattle egrets are cool. They share a symbiotic relationship with cattle. So these birds are often found right alongside cattle, and you can often see pictures of them actually resting on cattle's backs. What these birds do is follow cattle and other large mammals around a pasture, and when the animals move through, they disturb the grass and insects and other things that the cattle egret is trying to eat.

Dr. Joe Armstrong:

So as the cattle move, these birds are following right alongside them, eating things that become available because the cattle are moving through the grass. This is mostly just to demonstrate how closely some birds and livestock interact. Now having that background, we also have data that tells us that we have positive detections of high path avian influenza in cattle egrets in Egypt. We also have data that tell us that high path avian influenza, when inoculated into cattle egrets, acts like high path avian influenza, and many of those egrets die. There is also a study in Egypt looking at seroprevalence, or looking at serology, from many different species in Egypt and whether or not they have seroconverted to high path avian influenza.

Dr. Joe Armstrong:

In that study in 2013, all of the ruminants in that study did not have any seroconversion to high path avian influenza. That included cattle, buffalo, sheep, and goats. We did have seroconversion in horses, donkeys, and humans. So, again, all of that combined is telling me that something is different about cattle. Something is special, which I really, truly want to believe, but is actually true.

Dr. Joe Armstrong:

So if you've made it this far, congratulations for working through that paper with me and hanging in there through that experience. Let's get to my thoughts on all of this when we add it up and with all this reading looking at the history of influenza A in cattle, what does it mean? The big caveat to always say when we talk about influenza viruses is that they can change, and every time you think you've got them figured out, something changes. So we have to keep that in mind. This review paper is from 2019 that's already 5 years ago that's before we started to see this newest strain of high path avian influenza circulate in our wild birds and our domestic poultry.

Dr. Joe Armstrong:

I am personally taking some comfort in the fact that we have previous evidence of influenza A in cattle and it potentially causing disease without that being followed by an endemic status of the virus or any human health concerns that we know of. There's still a lot to do and a lot to learn. One of the major things that we have not done at this time, April 5th, is definitively connected the dots between the virus and the illness. We still don't know, for sure, if the virus is causing the illness. Until we get that, we really can't get ahead of ourselves too far.

Dr. Joe Armstrong:

The purpose of today was to give you more information, more background, allow you to draw some conclusions from what I've read, and hopefully condense it so you're not stuck reading the 32 pages for this review paper. I'll leave it there. If you have comments, questions, scathing rebuttals, those go to themoosroom@umn.edu. If you wanna call me, 612-624-3610. Check out our website, extension.umn.edu.

Dr. Joe Armstrong:

Thank you for listening today. I hope this was helpful. Hang in there. I'll talk to you soon.